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PURPOSE: Chronic granulomatous disease (CGD) is an inherited immunodeficiency caused by pathogenic variants of genes encoding the enzyme complex NADPH oxidase. In countries where tuberculosis (TB) is endemic and the Bacillus Calmette-Guérin (BCG) vaccine is routinely administered, mycobacteria are major disease-causing pathogens in CGD. However, information on the clinical evolution and treatment of mycobacterial diseases in patients with CGD is limited. The present study describes the adverse reactions to BCG and TB in Mexican patients with CGD. METHODS: Patients with CGD who were evaluated at the Immunodeficiency Laboratory of the National Institute of Pediatrics between 2013 and 2024 were included. Medical records were reviewed to determine the clinical course and treatment of adverse reactions to BCG and TB disease. RESULTS: A total of 79 patients with CGD were included in this study. Adverse reactions to BCG were reported in 55 (72%) of 76 patients who received the vaccine. Tuberculosis was diagnosed in 19 (24%) patients. Relapse was documented in three (10%) of 31 patients with BGC-osis and six (32%) of 19 patients with TB, despite antituberculosis treatment. There was no difference in the frequency of BCG and TB disease between patients with pathogenic variants of the X-linked CYBB gene versus recessive variants. CONCLUSIONS: This report highlights the importance of considering TB in endemic areas and BCG complications in children with CGD to enable appropriate diagnostic and therapeutic approaches to improve prognosis and reduce the risk of relapse.

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More frequent among adults, phenocopies may be caused by somatic mutations or anti-cytokine autoantibodies, mimicking the phenotypes of primary immunodeficiencies. A fourteen-year-old girl was referred for a two-year history of weight loss and multiple recurrent abscesses, complicated recurrent pneumonia, pyelonephritis, osteomyelitis, and septic shock, without fever. She had started with nausea, hyporexia, and weight loss, then with abscesses in her hands, knee, ankle, and spleen. She also developed a rib fracture and left thoracic herpes zoster. The patient was cachectic, with normal vital signs, bilateral crackles on chest auscultation, tumefaction of the knee joint, and poorly healed wounds in hands and chest, oozing a yellowish fluid. Chest computed tomography revealed multiple bilateral bronchiectases. Laboratory workup reported chronic anemia, leukocytosis, neutrophilia, mild lymphopenia, thrombocytosis, pan-hypergammaglobulinemia, and elevated acute serum reactants. Lymphocyte subsets were low but present. Mycobacterium tuberculosis was detected via polymerase chain reaction in a bone biopsy specimen from ankle osteomyelitis. Whole-exome sequencing failed to identify a monogenic defect. Interleukin-12 was found markedly elevated in the serum of the patient. Phosphorylation of STAT4, induced by increasing doses of IL-12, was neutralized by patient serum, confirming the presence of anti-IL12 autoantibodies. IL-12 and IL-23 are crucial cytokines in the defense against intracellular microorganisms, the induction of interferon-gamma production by lymphocytes, and other inflammatory functions. Patients who develop neutralizing serum autoantibodies against IL12 manifest late in life with weight loss, multiple recurrent abscesses, poor wound healing, and fistulae. Treatment with anti-CD20 monoclonal antibodies was effective.

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BACKGROUND: The severe pharmacodermias (SF) are associated with high morbidity and mortality. Chronic kidney failure (CKD) related with dialysis is one of the main factors associated with higher mortality. ABCD-10 is a predictive mortality scale that includes the history of dialysis. CASE REPORT: Male 2 years old with a history of CKD on peritoneal dialysis and Lennox-Gastaut syndrome, admitted to the hospital due to acute peritonitis and developed SJS-NET secondary to phenytoin administration. He was treated with immunoglobulin and systemic steroid without improvement. Septic shock was added, presenting a fatal outcome. CONCLUSIONS: In the case presented, the ABCD-10 scale was applied, reporting a greater prediction of mortality compared to SCORTEN due to a history of dialysis. In children with SF there are no validated predictive mortality. Future initiatives should search for risk factors for mortality in children who develop SF for the creation of a predictive mortality scale.

ANTECEDENTES: Las farmacodermias graves se asocian con alta morbilidad y mortalidad. La insuficiencia renal crónica relacionada con diálisis es uno de los principales factores asociados con mortalidad. REPORTE DE CASO: Paciente pediátrico masculino de 2 años, con antecedente de insuficiencia renal crónica (en tratamiento con diálisis peritoneal) y síndrome de Lennox-Gastaut, que ingresó al hospital por peritonitis aguda y evolucion a síndrome de Stevens-Johnson-necrólisis epidérmica tóxica, debido a la administración de fenitoína. Recibió tratamiento con inmunoglobulina y corticosteroide sistémico sin mejoría; se agregó choque séptico y posteriormente falleció. CONCLUSIONES: La escala ABCD-10 versus SCORTEN es más efectiva para predecir la mortalidad por antecedente de diálisis. En niños con farmacodermias graves no existen escalas predictoras de mortalidad validadas. Las futuras iniciativas deben buscar factores de riesgo de mortalidad en niños con farmacodermias graves para la creación de una escala predictora de mortalidad.

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BACKGROUND: WHIM syndrome corresponds to an inborn error of innate and intrinsic immunity, characterized by: warts (Warts), Hypogammaglobulinemia, Infections and Myelocathexis, for its acronym in English. CASE REPORT: 4-year-old male, with severe neutropenia and B-cell lymphopenia from birth, without severe infections or warts; the panel genetic sequencing study of primary immunodeficiencies with the CXCR4 c.1000C>T (p.Arg334*) variant, which is associated with WHIM syndrome. CONCLUSIONS: The diagnosis of severe neutropenia from birth should include the search for inborn errors of immunity, through genetic sequencing studies, especially in asymptomatic or oligosymptomatic patients.

ANTECEDENTES: El síndrome WHIM corresponde a un error innato de la inmunidad innata e intrínseca, caracterizada por verrugas (Warts), hipogammaglobulinemia, infecciones y mielocatexis, por sus siglas en inglés. REPORTE DE CASO: Paciente masculino de 4 años, con neutropenia severa y linfopenia de células B desde el nacimiento, sin infecciones severas ni verrugas. El estudio de secuenciación genética informó la variante CXCR4 c.1000C>T (p.Arg334*), relacionada con el síndrome de WHIM. CONCLUSIÓN: El diagnóstico de neutropenia severa desde el nacimiento debe incluir la búsqueda de errores innatos de la inmunidad, mediante estudios de secuenciación genética, especialmente en pacientes asintomáticos u oligosintomáticos.

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INTRODUCTION: Hyper-IgM syndrome is an innate error of immunity in which there is a defect in change of isotype of immunoglobulins, with decreased values of IgG, IgA, and IgE, but normal or increased level of IgM. This predisposes to infectious processes at the respiratory and gastrointestinal levels, as well as autoimmune diseases and neoplasm. CASE REPORT: A 5 year 7-month-old boy with a history of 2 pneumonias, one of them severe, and chronic diarrhea since he was 2 years old. Persistent moderate neutropenia decreased IgG and elevated IgM. Cytometry flow confirmed absence of CD40L. Clinical evolution with early hepatic involvement. DISCUSSION: Hyper-IgM syndrome predisposes to liver damage, so a complete evaluation is required as well as early diagnosis. Active anti-infective treatment and control of the inflammatory response are key to the treatment of liver damage.

INTRODUCCIÓN: El síndrome de hiper-IgM es un error innato de la inmunidad, caracterizado por un defecto en el cambio de isotipo de inmunoglobulina, con valores disminuidos de IgG, IgA e IgE, y concentraciones normales o elevadas de IgM. Predispone a procesos infecciosos en el sistema respiratorio y aparato gastrointestinal, además de enfermedades autoinmunes y neoplasias. REPORTE DE CASO: Paciente pediátrico de género masculino, de 5 años y 7 meses de edad, con antecedente de dos cuadros de neumonía (uno de estos grave) y diarrea crónica desde los 2 años. Neutropenia moderada persistente, disminución de la concentración de IgG y elevación de IgM. La citometría de flujo confirmó la ausencia de CD40L. Durante la evolución clínica tuvo afectación hepática temprana. CONCLUSIÓn: El síndrome de hiper-IgM predispone a daño hepático, por lo que se requiere la evaluación completa y el diagnóstico oportuno. El tratamiento antiinfeccioso activo y el control de la respuesta inflamatoria son factores decisivos para establecer el tratamiento del daño hepático.

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BACKGROUND: The Pfizer-BioNTech® BNT162b2 vaccine, provides 95% effectiveness from the second dose onwards. The reported rate of anaphylaxis to COVID-19 vaccines is 4.7 cases/million doses administered. CASE REPORT: 30-year-old female, health professional, history of allergic rhinitis, asthma, reaction to eye cosmetics and adhesive tape: erythema, edema, and local pruritus. Immediately after application of the first dose of Pfizer-BioNTech vaccine, she presented grade III anaphylaxis. The patient was stratified, phenotyped and skin tests with PEG 3350 were positive. A recommendation was issued not to reapply vaccine containing polyethylene glycol and alternatives were offered. CONCLUSIONS: An adequate risk stratification should be performed before applying mRNA-based COVID-19 vaccines for the first time in at-risk groups. In case of anaphylaxis at the first dose, phenotyping and further study with PEG skin tests should be performed and vaccination alternatives should be offered.

INTRODUCCIÓN: La vacuna Pfizer-BioNTech® BNT162b2 proporciona efectividad del 95% a partir de la segunda dosis. La tasa de anafilaxia reportada de vacunas para COVID-19 es de 4.7 casos por millón de dosis administradas. REPORTE DEL CASO: Paciente femenina de 30 años, profesional de la salud, con antecedentes de rinitis alérgica, asma, reacción a productos cosméticos en los párpados y al pegamento de la cinta adhesiva (eritema, edema y prurito local). Posterior a la aplicación de la primera dosis de la vacuna Pfizer-BioNTechÒ tuvo un evento de anafilaxia grado III. Se estratificó, fenotipificó y efectuaron pruebas cutáneas con PEG-3350, que resultaron positivas. Se sugirió no aplicar la aplicar vacuna de refuerzo que contuviera polietilenglicol y se ofrecieron alternativas de tratamiento. CONCLUSIONES: Es importante efectuar la adecuada estratificación de riesgo antes de aplicar las vacunas para COVID-19 basadas en ARNm por primera vez. En caso de anafilaxia es necesario fenotipificar y ampliar el estudio con pruebas cutáneas con PEG, además de otorgar alternativas de vacunación.

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Mutations in recombinase activating genes 1 and 2 (RAG1/2) result in human severe combined immunodeficiency (SCID). The products of these genes are essential for V(D)J rearrangement of the antigen receptors during lymphocyte development. Mutations resulting in null-recombination activity in RAG1 or RAG2 are associated with the most severe clinical and immunological phenotypes, whereas patients with hypomorphic mutations may develop leaky SCID, including Omenn syndrome (OS). A group of previously unrecognized clinical phenotypes associated with granulomata and/or autoimmunity have been described as a consequence of hypomorphic mutations. Here, we present six patients from unrelated families with missense variants in RAG1 or RAG2. Phenotypes observed in these patients ranged from OS to severe mycobacterial infections and granulomatous disease. Moreover, we report the first evidence of two variants that had not been associated with immunodeficiency. This study represents the first case series of RAG1- or RAG2-deficient patients from Mexico and Latin America.

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BACKGROUND: Allergen immunotherapy (AIT) has a longstanding history and still remains the only disease-changing treatment for allergic rhinitis and asthma. Over the years 2 different schools have developed their strategies: the United States (US) and the European. Allergen extracts available in these regions are adapted to local practice. In other parts of the world, extracts from both regions and local ones are commercialized, as in Mexico. Here, local experts developed a national AIT guideline (GUIMIT 2019) searching for compromises between both schools. METHODS: Using ADAPTE methodology for transculturizing guidelines and AGREE-II for evaluating guideline quality, GUIMIT selected 3 high-quality Main Reference Guidelines (MRGs): the European Academy of Allergy, Asthma and Immunology (EAACI) guideines, the S2k guideline of various German-speaking medical societies (2014), and the US Practice Parameters on Allergen Immunotherapy 2011. We formulated clinical questions and based responses on the fused evidence available in the MRGs, combined with local possibilities, patient's preference, and costs. We came across several issues on which the MRGs disagreed. These are presented here along with arguments of GUIMIT members to resolve them. GUIMIT (for a complete English version, Supplementary data) concluded the following. RESULTS: Related to the diagnosis of IgE-mediated respiratory allergy, apart from skin prick testing complementary tests (challenges, in vitro testing and molecular such as species-specific allergens) might be useful in selected cases to inform AIT composition. AIT is indicated in allergic rhinitis and suggested in allergic asthma (once controlled) and IgE-mediated atopic dermatitis. Concerning the correct subcutaneous AIT dose for compounding vials according to the US school: dosing tables and formula are given; up to 4 non-related allergens can be mixed, refraining from mixing high with low protease extracts. When using European extracts: the manufacturer's indications should be followed; in multi-allergic patients 2 simultaneous injections can be given (100% consensus); mixing is discouraged. In Mexico only allergoid tablets are available; based on doses used in all sublingual immunotherapy (SLIT) publications referenced in MRGs, GUIMIT suggests a probable effective dose related to subcutaneous immunotherapy (SCIT) might be: 50-200% of the monthly SCIT dose given daily, maximum mixing 4 allergens. Also, a table with practical suggestions on non-evidence-existing issues, developed with a simplified Delphi method, is added. Finally, dissemination and implementation of guidelines is briefly discussed, explaining how we used online tools for this in Mexico. CONCLUSIONS: Countries where European and American AIT extracts are available should adjust AIT according to which school is followed.

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BACKGROUND: Primary immunodeficiencies are diseases that are caused by one or more defects in the immune system. OBJECTIVE: The purpose of the article is to describe the characteristics of the immunodeficiencies that were diagnosed in a pediatric hospital, which forms a reference center in the West of Mexico. METHODS: A cross-sectional study of pediatric patients with primary immunodeficiency in a pediatric hospital in Guadalajara, Jalisco. RESULTS: 60 patients were registered, of which 21% were female, and 78% were male. Predominant immunodeficiencies of antibodies formed the largest group (46% of patients). X-linked agammaglobulinemia was the most frequent immunodeficiency (21%); other frequent diagnoses were common variable immunodeficiency, and IgG subclass deficiency. The average age of the patients that were diagnosed was of 6.3 years. The most common initial manifestations were infectious processes (46%), and pneumonia was the frequent diagnosis (30%). Autoimmune manifestations were observed in 13% of patients; 67% of the patients were found with immunoglobulin replacement therapy, with which a decrease in hospitalizations from 3.2 times to 0.13 times was observed. There were two deceased patients due to surgical complications of cardiac correction and intestinal reconnection. CONCLUSION: Knowing the behavior of primary immune deficiencies in our environment allows the opening of areas of opportunity in order to improve the survival and quality of life of our patients.

Antecedentes: Las inmunodeficiencias primarias son un grupo de enfermedades causadas por uno más defectos del sistema inmunitario. Objetivo: Describir las características de las inmunodeficiencias diagnosticadas en un hospital pediátrico de tercer nivel, que constituye un centro de referencia en el Occidente de México. Métodos: Estudio transversal de pacientes pediátricos con inmunodeficiencias primarias atendidos en un hospital pediátrico en Guadalajara, Jalisco. Resultados: Se registraron 60 pacientes, 21 % mujeres y 78 % hombres. Las inmunodeficiencias predominantes de anticuerpos constituyeron el grupo más numeroso (46 %). La agammaglobulinemia ligada al cromosoma X fue la inmunodeficiencia más frecuente, con 21 % del registro. Otros diagnósticos frecuentes fueron inmunodeficiencia común variable y deficiencia de subclases de IgG. El promedio de edad al diagnóstico fue de 6.3 años. Las manifestación inicial más común fueron los procesos infecciosos (46 %) y la neumonía fue el diagnóstico más frecuente (30 %). Las manifestaciones autoinmunes se observaron en 13 % de los pacientes; 67 % de los pacientes se encontró con sustitución de inmunoglobulina, con la cual se observó disminución en las hospitalizaciones: de 3.2 a 0.13 veces. Fallecieron dos pacientes por complicaciones quirúrgicas de corrección cardiaca y reconexión intestinal. Conclusión: El conocimiento del comportamiento de las inmunodeficiencias primarias en nuestro medio permite apertura de áreas de oportunidad a fin de mejorar la supervivencia y calidad de vida de los pacientes.

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